Case Study 56
Kenneth Clark, MD
Question 1
• This is a 59-year-old Caucasian woman with a
history of granulomatous nephritis (diagnosed 7
years prior), myelodysplastic syndrome, and
common variable immunodeficiency with
progressively worsening dizziness, blurry vision
and headache. Workup at an outside hospital
revealed a “sellar mass” along with
panhypopituitarism, adrenal insufficiency and
hypothyroidism.
• Describe the MRI findings.
Axial T1
Axial T2
Axial T1 + Contrast
Axial T2 FLAIR
Answer
• Symmetric enlargement of pituitary gland and
infundibulum with mild homogeneous
enhancement. No areas of T2 or T2 FLAIR
signal abnormality are evident.
Question 2
• What is the differential diagnosis of a sellar
lesion?
Answer
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Pituitary Adenoma
Craniopharyngioma
Meningioma
Pituitary Carcinoma
Pituicytoma
Oncocytoma
Granular Cell Tumor
Lymphocytic Hypophysitis
Granulomatous Hypophysitis
Metastatic Disease (rare)
Question 3
• What are the common signs and symptoms of
sellar lesions (tumors or inflammatory)?
Answer
• Headaches (non-specific)
• Double Vision (non-specific)
• Loss of Peripheral Vision – Bitemporal
Hemianopsia (non-specific)
• Facial Pain and Numbness (non-specific)
• Symptoms related to hormonal abnormalities
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lack of energy
weight loss, nausea, vomiting, constipation
amenorrhea and infertility
dry skin, increased pigmentation of the skin
cold intolerance
mental status changes: sleepiness, psychosis
Question 4
• The lesion was resected. Describe the findings.
• Click here to view the slide
Answer
• The tissue shows near complete effacement of pituitary
architecture by a rich lymphohistiocytic infiltrate. The
histiocytes have large irregularly shaped nuclear with
prominent nucleoli and finely distributed pale blue
chromatin. The cytoplasmic borders are completely
indistinct, resulting in a syncytial appearance of groups
of histiocytes. Small numbers of small monomorphic
lymphocytes are positioned around the periphery of the
histiocyte collections. Small randomly isolated nests of
polytypic pituitary cells are seen randomly distributed
throughout the specimen.
Question 5
• What is your diagnostic impression?
Answer
• The lesion appears to be inflammatory in nature
rich in histiocytes – either infectious or idiopathic
in etiology. It does not appear to be neoplastic,
although lymphoma cannot be entirely ruled out
at this point.
Question 6
• What immunohistochemical and/or special stains
would be helpful in confirming your initial
impression of this lesion?
Answer
• Inflammatory Cell Markers
– CD3 (T-cells)
– CD20 (B-cells)
– CD68 (macrophages, histiocytes)
• GFAP, IDH1 (to rule out an unusual glial process)
• Synaptophysin (to ascertain the pituitary element)
• Reticulin (to evaluate residual pituitary
structure/architecture)
• Click to view CD3, CD68, Reticulin
Question 7
• Based on the results of the stains (see below)
and H&E slides, what is the general diagnostic
category?
• CD3 - highlights numerous small mature lymphocytes
• CD20 - very rare positive b-lymphocytes
• CD68 - strong staining in numerous histiocytes; highlights ill-defined
granuloma formation
• Synaptophysin - positive in sparse scattered small nests of pituitary
cells; highlights architectural distortion by histiocytes
• GFAP - rare positive glial cells near periphery of lesion
• IDH1 - negative
• Reticulin – highlights total effacement of nested pituitary architecture
Answer
• Inflammatory/histiocytic process
Question 8
• What is the differential diagnosis of a nonnecrotizing histiocytic / granulomatous process?
Answer
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Neurosarcoidosis
Infectious (fungal or mycobacterial)
Langerhans cell histiocytosis
Erdheim Chester disease
Rosai-Dorfman disease
Question 9
• What additional stains would you order to better
characterize the lesion?
Answer
• Acid Fast, Grocott (rule out infectious process)
• CD1A & S100
– Langerhans cell histiocytosis: histiocytes are CD1a
and S100 positive
– Erdheim Chester disease: histiocytes are S100
negative (usually) and CD1a negative
– Rosai Dorfman disease: histiocytes are S100 positive
and CD1a negative
– Sarcoidosis has similar staining profile of ECD
Question 10
• The results of the additional stains are as
follows:
– S100: shows sparsely scattered background
folliculo-stellate cells; negative in histiocytes
– CD1a: negative
– Grocott: negative
– Acid Fast: negative
• What is your diagnosis?
Answer
• Non-necrotizing granulomatous hypophysitis,
favor neurosarcoidosis
Question 11
• Why favor sarcoidosis when Erdheim Chester
disease has a similar histologic appearance and
immunohistochemical profile? Explain.
Answer
• ECD, which is far more rare than sarcoidosis (300-400
reported cases worldwide), is also called polyostotic
sclerosing histiocytosis because it most often involves
long bones. Because this patient had a history of nonnecrotizing renal granulomas and no bone lesions it is
much more likely that this represents sarcoidosis
involving the pituitary than ECD. Furthermore, ECD has
a progressive and usually fatal course in cases with
extra-osseous involvement and is not responsive to
steroid therapy; if this patient had ECD at the time of her
renal biopsies her clinical course would likely have been
much more aggressive and probably fatal. Histologically,
ECD lesions often show Touton-like giant cells and are
rich in eosinophils – neither of which are seen in this
lesion. Considering the clinical AND histopathologic
elements of this case, it seems that sarcoidosis is more
likely than ECD.
References
• Veyssier-Belot C, Cacoub P, Caparros-Lefebvre D, Wechsler J,
Brun B, Remy M, Wallaert B, Petit H, Grimaldi A, Wechsler B,
Godeau P (1996) Erdheim–Chester disease. Clinical and Radiologic
Characteristics of 59 Cases. Medicine (Baltimore). 75:157–169.
• Louis D, Ohgaki H, Wiestler O, Cavanee W. WHO Classification of
Tumours of the Central Nervous System. IARC: Lyon 2007.
• Burns T. Neurosarcoidosis (2003). Arch Neurol. 60:1166-1168.
• Rosai J. Rosai and Ackerman’s Surgical Pathology. Elsevier 2004.